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Effect of codeine on CYP450 isoform activity of rats

Context: Codeine, also known as 3-methylmorphine, is an opiate used to treat pain, as a cough medicine and for diarrhoea. No study on the effects of codeine on the metabolic capacity of CYP enzyme is reported. Objective: In order to investigate the effects of codeine on the metabolic capacity of cyt...

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Autores principales: Wang, Shuanghu, Dong, Yanwen, Su, Ke, Zhang, Jing, Wang, Linyi, Han, Anyue, Wen, Congcong, Wang, Xianqin, He, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130733/
https://www.ncbi.nlm.nih.gov/pubmed/28253826
http://dx.doi.org/10.1080/13880209.2017.1297466
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author Wang, Shuanghu
Dong, Yanwen
Su, Ke
Zhang, Jing
Wang, Linyi
Han, Anyue
Wen, Congcong
Wang, Xianqin
He, Yan
author_facet Wang, Shuanghu
Dong, Yanwen
Su, Ke
Zhang, Jing
Wang, Linyi
Han, Anyue
Wen, Congcong
Wang, Xianqin
He, Yan
author_sort Wang, Shuanghu
collection PubMed
description Context: Codeine, also known as 3-methylmorphine, is an opiate used to treat pain, as a cough medicine and for diarrhoea. No study on the effects of codeine on the metabolic capacity of CYP enzyme is reported. Objective: In order to investigate the effects of codeine on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B1, CYP2D1, CYP1A2, CYP3A2 and CYP2C11. Materials and methods: Sprague–Dawley rats were randomly divided into codeine group (low, medium, high) and control group. The codeine group rats were given 4, 8, 16 mg/kg (low, medium, high) codeine by continuous intragastric administration for 14 days. Five probe drugs bupropion, metroprolol, phenacetin, midazolam and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Results and conclusion: The pharmacokinetic parameters of bupropion and metroprolol experienced obvious change with AUC((0-t)), C(max) increased and CL decreased for bupropion in medium dosage group and midazolam low dosage group. This result indicates that the 14 day-intragastric administration of codeine may inhibit the metabolism of bupropion (CYP2B1) and midazolam (CYP3A2) in rat. Additional, there are no statistical differences for albumin (ALB), alkaline phosphatase (ALP), creatinine (Cr) after 14 intragastric administration of codeine, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) increased compared to control group. The biomedical test results show continuous 14 day-intragastric administration of codeine would cause liver damage.
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spelling pubmed-61307332018-09-27 Effect of codeine on CYP450 isoform activity of rats Wang, Shuanghu Dong, Yanwen Su, Ke Zhang, Jing Wang, Linyi Han, Anyue Wen, Congcong Wang, Xianqin He, Yan Pharm Biol Research Article Context: Codeine, also known as 3-methylmorphine, is an opiate used to treat pain, as a cough medicine and for diarrhoea. No study on the effects of codeine on the metabolic capacity of CYP enzyme is reported. Objective: In order to investigate the effects of codeine on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B1, CYP2D1, CYP1A2, CYP3A2 and CYP2C11. Materials and methods: Sprague–Dawley rats were randomly divided into codeine group (low, medium, high) and control group. The codeine group rats were given 4, 8, 16 mg/kg (low, medium, high) codeine by continuous intragastric administration for 14 days. Five probe drugs bupropion, metroprolol, phenacetin, midazolam and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Results and conclusion: The pharmacokinetic parameters of bupropion and metroprolol experienced obvious change with AUC((0-t)), C(max) increased and CL decreased for bupropion in medium dosage group and midazolam low dosage group. This result indicates that the 14 day-intragastric administration of codeine may inhibit the metabolism of bupropion (CYP2B1) and midazolam (CYP3A2) in rat. Additional, there are no statistical differences for albumin (ALB), alkaline phosphatase (ALP), creatinine (Cr) after 14 intragastric administration of codeine, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) increased compared to control group. The biomedical test results show continuous 14 day-intragastric administration of codeine would cause liver damage. Taylor & Francis 2017-03-02 /pmc/articles/PMC6130733/ /pubmed/28253826 http://dx.doi.org/10.1080/13880209.2017.1297466 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Shuanghu
Dong, Yanwen
Su, Ke
Zhang, Jing
Wang, Linyi
Han, Anyue
Wen, Congcong
Wang, Xianqin
He, Yan
Effect of codeine on CYP450 isoform activity of rats
title Effect of codeine on CYP450 isoform activity of rats
title_full Effect of codeine on CYP450 isoform activity of rats
title_fullStr Effect of codeine on CYP450 isoform activity of rats
title_full_unstemmed Effect of codeine on CYP450 isoform activity of rats
title_short Effect of codeine on CYP450 isoform activity of rats
title_sort effect of codeine on cyp450 isoform activity of rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130733/
https://www.ncbi.nlm.nih.gov/pubmed/28253826
http://dx.doi.org/10.1080/13880209.2017.1297466
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